AJP - Cell Physiology, Vol 258, Issue 3 C377-C389, Copyright © 1990 by American Physiological Society
Regulation of oxidative phosphorylation in the mammalian cell
R. S. Balaban
Laboratory of Cardiac Energetics, National Institutes of Health, Bethesda, Maryland 20892.
The cell is capable of maintaining a steady-state flux of energy from
mitochondrial oxidative phosphorylation, producing ATP, to the cytosolic
adenosinetriphosphatases (ATPases), performing work. Considerable effort
has been devoted to investigating the individual mechanisms involved in
these two processes. However, less effort has been directed toward learning
how these reactions of energy metabolism interact through the cytosol to
maintain the observed steady state in the intact cell. The "classical"
model for the cytosolic interaction of these two processes involves the
feedback of ATP hydrolysis products, ADP and Pi, from the ATPases to
oxidative phosphorylation. This model is based on data from isolated
mitochondria in which the rate of oxidative phosphorylation is controlled
by the concentration of ADP and Pi. Yet, recent data from intact tissues
with high oxidative phosphorylation capacities (i.e., heart, brain, and
kidney) indicate that the cytosolic concentration of ADP and Pi do not
change significantly with work. These data imply that this simple feedback
model is not adequate to explain the regulation of energy metabolism in
these tissues. Other sites within the oxidative phosphorylation process
must be playing a regulatory role or the kinetics of ATP synthesis must be
very different than currently believed to establish the steady state. This
review covers the potential sites within oxidative phosphorylation which
may be regulated through cytosolic transducers to result in the necessary
feedback network regulating the steady-state flow of energy in the cell.
These sites will include substrate delivery to the cytochrome chain, the
processes involved in the phosphorylation of ADP to ATP, and the delivery
of oxygen.
